Bromo group

Intramolecular nucleophilic displacement of the bromo group by an azine-nitrogen occurs in the cyclization of A-2-quinaldyl-2-bromo-pyridinium bromide (248) to give the naphthoimidazopyridinium ring system. The reaction of 2-bromopyridine and pyridine 1-oxide yields l-(2-pyridoxy)pyridinium bromide (249) which readily undergoes an intramolecular nucleophilic substitution in which departure of hydrogen as a proton presumably facilitates the formation of 250 by loss of the JV-oxypyridyl moiety. 

Aminodebromination of 4-bromo-l//-3-benzazepin-2-amine (25) with triethylamine occurs readily and results in formation of the quaternary salt 26 (see also Section 3.2.1.5.6.), whereas attempts to effect nucleophilic substitution of bromide with primary or secondary amines gives only tarry mixtures.41 The bromo group is also resistant to displacement by azide and benz-cncthiolate but undergoes substitution with thiocyanate ion in hot dimethylformamide to give the 4-thiocyanato derivative 27 rather than the thiourea by addition at the amine function. 

When heated under reflux in 48% hydrobromic acid 4-bromo-2(3W)-benzothiazolones rearranged to the 6-bromo isomers (41). The mechanism is believed to involve initial protonation at C-4, followed by either bromide ion attack at C-6 (with concomitant SN2 expulsion of the 4-bromine), or bromide attack at the 4-bromo group to remove it as molecular bromine. Subsequent electrophilic bromination at the 6-position is then possible. The latter process is favored by the authors. Further bromination of 41 gave a 32% yield of the 4,6-dibromobenzothiazolone (91T2255) (Scheme 26). 

The reaction rate is greatly enhanced by substitution in the 6 position of the attacking ring, for steric reasons. For example, a methyl, chloro, or bromo group in... 

An important use of the dediazoniation reaction is to remove an amino group after it has been used to direct one or more other groups to ortho and para positions. For example, the compound 1,3,5-tribromobenzene cannot be prepared by direct bromination of benzene because the bromo group is ortho-para directing however, this compound is easily prepared by the following sequence ... 

The reaction of 2-bromo-5-nitrothiazole with weakly basic secondary aliphatic amines gave the expected 2-amino products. The isomeric 5-bromo-2-nitrothiazole with such amines gave mixtures of the expected 5-amino products along with 2-aminated 5-nitrothiazole rearrangement products. A mechanism was proposed which involves the slow thermal isomerisation of the 5-bromo-2-nitrothiazole to the much more reactive 2-bromo isomer which competes, in the case of relatively weak amine nucleophiles, with direct but slow displacement of the 5-bromo group to form the normal displacement product <96JHC1191>. 

Reaction of 47 with NBS in carbon tetrachloride afforded the tribromide (240, 100%). After replacement of the primary bromo group with benzoyl-oxyl, the product (241,47%) was debrominated with zinc dust in ethanol to give the diene (242,64%). Epoxidation of242 produced the isomeric compounds 243 and 244, which were transformed into the azides (245 and 246), convertible into valienamine isomers. ... 

DL-Valiolamine (205) was synthesized from the exo-alkene (247) derived from 51 with silver fluoride in pyridine. Compound 247 was treated with a peroxy acid, to give a single spiro epoxide (248, 89%) which was cleaved by way of anchimeric reaction in the presence of acetate ion to give, after acetylation, the tetraacetate 249. The bromo group was directly displaced with azide ion, the product was hydrogenated, and the amine acety-lated, to give the penta-A, 0-acetyl derivative (250,50%). On the other hand. 

Sharpless reaction of the enantiomeric alkenes (47) produced the precursors for 2-amino-2-deoxy-o -D and -L-carba-glucopyranoses. These compounds were converted into the penta-7V,0-acetates by the following sequence. Replacement of the bromo group with an acetate ion, treatment with sodium in liquid ammonia, and peracetylation. 

DMA. Introduetion of a 5-methyl or 5-bromo group, to produce 5-methyl-2,4-DMA and 5-bromo-2,4-DMA, results in active agents, but they are not signifieantly more potent than 2,4-DMA itself. It seems that the methyl and bromo substituents are tolerated at the 5-position, but they do not produce the increase in activity seen in the 2,5-DMA series. 

Otera et al. extended the tin-mediated allylation to 2-substituted allyl bromides.80 When 2-bromo and 2-acetoxy-3-bromo-l-propene were used, the allylation with tin produced the corresponding functionalized coupling products (Eqs. 8.36 and 8.37). In the case of 2,3-dibromopropene, the reaction occurred exclusively through allylation in the presence of the vinyl bromo group. The presence of other electrophiles such as a nitrile (-CN) or an ester (-COOR) did not interfere with the reaction. 

In order to isolate a single isomer of diphosphathienoquinone, two bromo groups were attached to 3,4-positions to avoid formation of the ( )-form by steric repulsion between Br and Mes groups. Analogous dehydrochlorination of the precursor afforded (Z,Z)-diphosphathienoquinone 4b as a single isomer (Scheme 11) [11], Diphosphathienoquinone 4b did not undergo iiZ-isomerization either under thermal or under photolytical condition. 

The pyrimido[l,6- ]pyrimidines 68 could be brominated at the reactive 9-position. The bromo group of the resulting 69 was exchanged for a thiol group in 70 (Scheme 8). The thiol 70 reacted with 69 in NaOMe/EtOH/ dioxane to give the 9,9 -thiobis derivative 38 in 88% yield <1999JHC453>. 

Bis(pinacolato)diboron reacts with 1-halo-l-lithioalkenes, that is, alkylidene carbenoids, affording 1,1-diboryl-1-alkenes in good yields (Scheme 9).76 The reaction proceeds via formation of a borate intermediate, which is followed by 1,2-migration of the boryl group with elimination of the bromo group. 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

Mannschreck et al. (44) examined the effect of substituents on the barriers to rotation in 2,4,6-trisubstituted benzamides. In /V-benzyl-A(-methyl-2,4,6-tri-bromobenzamide, the rotational barrier (AG ) is 23.8 kcal/mol at 35.8 to 40.6°C for the Z -> E process in quinoline (44). This should be compared with AG of 23.4 kcal/mol for the same process with the trimethyl compound (5). It is seen that steric effects are of primary importance, inasmuch as the van der Waals radii of the methyl and bromo groups are almost the same. 

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